This proposal details methods for attaching toxic ricin A chain via disulfide linkage to both vibalent and monovalent antibody carriers. This mode of coupling mimics connection to its natural carrier subunit, ricin B chain, and thus high cytotoxic potency is retained while the precise specificity characteristics of antibody are acquired. Non-specific toxicity is precluded since surface binding of the A chin is focused exclusively to cells bearing the chosen antigenic determinant and internalization is required before it can exert its effect on ribosomes. Distinct monoclonal antibodies directed against human immunoglobulin lambda, kappa, gamma and delta chain deterinants as well as against the human acute lymphoblastic leukemia antigen, will be conjugated with ricin A chain. Hybridoma derived antibodies directed against idiotypic determinants of human Ig on malignant B cells will be produced and similarly deployed as a tumor-directed A chain vehicle. Experiments with human antigen bearing target cell lines will be performed to judge the potency and specificity of these conjugates in vitro. Factors which influence the uptake into cells will be examined and the effect of these cytotoxins on cell cycle kinetics will be analyzed. Furthermore, their effectiveness in vivo will be evaluated using human tumor cell lines heterotransplanted into nude mice. This study will thus permit a preliminary assessment of the potential value of antibody-ricin A chain conjugates for future application to therapeutic problems in man.